Adult T- cell leukemia/lymphoma (ATL), a mature T-cell derived neoplasm with leukemic lymphoma nature is characterized by massive leukemic cell infiltration into various organs. Cutaneous involvement and hepatosplenomegaly are common manifestations; thyroid involvement and its association with papillary thyroid carcinoma (PTC) are rare. Role of fine needle aspiration cytology (FNAC) in primary diagnosis of thyroid cancers, especially lymphoid neoplasms has been well documented. With the aid of immunocytochemistry, flow cytometry, deoxyribonucleic acid analysis and immunophenotyping, thyroid lymphoid neoplasms are treated with chemoradiation, bypassing the need for surgical intervention. However, the non-diagnostic sampling error rate is relatively high or remains undiagnosed as lymphocytic thyroiditis (LT).
A 55-year-old lady was admitted with a slowly progressing thyroid mass of 20 years duration associated with a recent onset of fever. There was no history of dysphagia, hoarseness of voice, weight loss or toxic symptoms. The mass was non-tender, 5cms x 5cms in size, nodular and hard. There was generalized lymphadenopathy involving bilateral cervical, axillary and inguinal nodes.
A fine needle aspiration of the thyroid mass and left cervical lymph node yielded blood tinged material. The thyroid aspiration smears showed follicular cells in papillary fronds, in groups, clusters and scattered singly. The nuclei were overlapping and had fine chromatin, grooves and intranuclear inclusionsa. The background was hemorrhagic with an infiltrate of lymphocytes, plasma cells and atypical cleaved lymphoid cells, similar to the reactive infiltrate of LT. The cytological features were of PTC accompanied by a suspicious lymphoma infiltrate. The cervical node aspiration smears were moderately cellular comprising of a monotonous population of atypical lymphoid cells, with scanty cytoplasm, clefted nuclei and coarse clumped chromatin consistent with lymphoma cells. Correlating both the cytological pictures, a diagnosis of combined PTC and thyroid lymphoma was made.
Investigating further, indirect laryngoscopy showed both the vocal cords moving with respiration and phonation. Ultrasonography of the neck revealed enlarged thyroid with heterogeneous echotexture and multiple large nodules with calcification and few cystic spaces and increased vascularity on Doppler scan. Bilateral level Ib, II, III, IV, V and VI nodes were enlarged with absent hilus, irregular borders and few showing necrosis, calcification and subcapsular vascularity. On computed tomography (CT) scan, the thyroid mass was predominantly in the isthmus and left lobe enlarged nodes were detected in the superior mediastinum, pretracheal, paratracheal, tracheobronchial, costopulmonary and subcarinal regions. A small nodule in the apical segment of left lower lobe of lung was suggestive of metastasis. The bone scan was normal and there was no hepatosplenomegaly or retroperitonal lymphadenopathy.
Laboratory investigations revealed hemoglobin of nine gm/dl and leukocytosis of 98,000cells/mm with 48% atypical lymphoid cells. Bone marrow aspiration and biopsy done showed diffuse involvement by cleaved lymphoma cells. Immunohistochemistry showed positivity with CD 45 and CD 3, confirming the T- cell origin; serological test for human T- cell leukemia virus type 1 (HTLV-1) antibody was negative. The patient was diagnosed as stage IV non-HTLV-1 ATL coexistent with PTC. She received chemotherapy comprising of six cycles of CHOP [cyclophosphomide, doxorubicin, vincristine, prednisolone]. During the course of treatment, she had pneumonia in the third month which was treated; the blood counts dropped to normal limits. At the end of the sixth cycle, the total leukocyte count was 9,800 cells /mm with platelet count of 2, 76,000 lakh /mm and hemoglobin of 11gm/dl. However, the repeat bone marrow aspiration and biopsy showed persistent lymphoma infiltration suggesting tumor progression; she is lost to follow-up since then.
Non-Hodgkin lymphoma involving the thyroid can be primary or secondary from local extension from adjacent neck nodes or metastasis from a distant site. These tumors are usually of B-cell lineage; T-cell lymphomas have also been described. ATL, caused by HTLV-1, is characterized by leukemic infiltration into various organs. The c-Met expression in ATL cells is considered significant in tumor invasion and metastasis.
The frequency of superimposed cancers, such as gastrointestinal adenocarcinomas, larynx cancers, hepatoma and thyroid papillary adenocarcinoma in ATL is significantly high. PTC occurring in combination with HTLV unassociated ATL, in fact being the primary clinical presentation, is rarely reported. The underlying pathophysiology is presumed to be one of the molecular defects. The somatic Fas mutations described in lymphoid neoplasms, including ATL, have been recently found significant in the pathogenesis of PTC.
Preoperative diagnosis of thyroid lymphoma/leukemia infiltrate is difficult on cytology owing to its resemblance to LT. Fewer numbers of follicular cells, Hürthle cells, tingible body macrophages and plasma cells favor a diagnosis of lymphoma. Lymphoid infiltrate per se has no statistical significance in differentiating the two conditions. Small, large and activated lymphoid cells with lymphoglandular bodies and plasma cells of LT can also be seen in mucosa associated lymphoid tissue (MALT) lymphomas while large cell lymphomas have a large monotonous population of neoplastic cells. The rate of false negative results with FNAC is frequent in lymphomas complicating LT due to sampling error or due to paucicellular aspirates. Diagnostic accuracy is more when neck nodes are involved. Other differential diagnoses include small cell variant of medullary carcinoma, metastatic small cell carcinoma of lung and anaplastic thyroid carcinoma. High grade lymphomas can be misinterpreted for anaplastic carcinomas resulting in unnecessary surgical intervention. In case of carcinomas, tumor cells are seen in clusters, staining positively with cytokeratin when compared to the dispersed pattern of lymphoma cells positive for lymphoid markers in the background of lymphoglandular bodies.
Autoimmune thyroiditis is considered the predisposing factor for PTC with risk rate of 10 to 40%, as evidenced by the presence of RET/PTC rearrangement in almost 95% of cases of Hashimoto thyroiditis. RET/PTC-1 activation either activates the follicular cells or provokes autoimmune responses that contribute to malignancy. A synchronous occurrence of PTC and non-HTLV-1 ATL as in the present case is very rare.
It was difficult to distinguish the primary or secondary thyroid involvement based on cytology alone. A thorough clinicoradiological examination for organomegaly and a complete hematological work-up is mandatory to identify the secondary lymphoma/leukemic infiltration. In our patient, it was the secondary involvement by adult T-cell leukemic infiltration. It was difficult to assess the nature of the background lymphoid infiltrate on cytology in the absence of prior history of LT or a systemic disease such as ATL.
For the diagnosis of thyroid lymphoma, surgery has limited value; most patients are treated by chemotherapy or radiation therapy. In the present case, a correct diagnosis obtained on FNAC avoided an unnecessary surgical intervention. Management of this patient was focused on thyroid lymphoma (stage IV) which has a worse prognosis compared to PTC with a relatively indolent course. Six cycles of chemotherapy normalized the peripheral blood cell counts. However, the overall prognosis is poor as evidenced by the persistent lymphoma infiltration of the marrow.
To summarize, critical evaluation of the lymphocyte-rich infiltrate of LT associated with PTC is important to identify rare T-cell lymphomas, primary or secondary, and distinguish them from the more frequent MALT lymphomas with better prognosis. FNAC is an easy, minimally invasive reliable initial diagnostic modality for thyroid lymphoid neoplasms and complementary cytopathologic techniques can increase the diagnostic accuracy bypassing surgery-asociated morbidity.
| How to cite this article: Khadilkar UN, Mathai AM, Chakrapani M, Prasad K. Rare association of papillary carcinoma of thyroid with adult T-cell lymphoma/leukemia. Indian J Pathol Microbiol 2010;53:125-7 |
| How to cite this URL: Khadilkar UN, Mathai AM, Chakrapani M, Prasad K. Rare association of papillary carcinoma of thyroid with adult T-cell lymphoma/leukemia. Indian J Pathol Microbiol [serial online] 2010 [cited 2010 May 14];53:125-7. Available from: http://www.ijpmonline.org/text.asp?2010/53/1/125/59202 |
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